| First Author | Liu XX | Year | 2022 |
| Journal | Signal Transduct Target Ther | Volume | 7 |
| Issue | 1 | Pages | 170 |
| PubMed ID | 35641478 | Mgi Jnum | J:352938 |
| Mgi Id | MGI:7642107 | Doi | 10.1038/s41392-022-00989-x |
| Citation | Liu XX, et al. (2022) BOD1 regulates the cerebellar IV/V lobe-fastigial nucleus circuit associated with motor coordination. Signal Transduct Target Ther 7(1):170 |
| abstractText | Cerebellar ataxias are characterized by a progressive decline in motor coordination, but the specific output circuits and underlying pathological mechanism remain poorly understood. Through cell-type-specific manipulations, we discovered a novel GABAergic Purkinje cell (PC) circuit in the cerebellar IV/V lobe that projected to CaMKIIalpha(+) neurons in the fastigial nucleus (FN), which regulated sensorimotor coordination. Furthermore, transcriptomics profiling analysis revealed various cerebellar neuronal identities, and we validated that biorientation defective 1 (BOD1) played an important role in the circuit of IV/V lobe to FN. BOD1 deficit in PCs of IV/V lobe attenuated the excitability and spine density of PCs, accompany with ataxia behaviors. Instead, BOD1 enrichment in PCs of IV/V lobe reversed the hyperexcitability of CaMKIIalpha(+) neurons in the FN and ameliorated ataxia behaviors in L7-Cre; BOD1(f/f) mice. Together, these findings further suggest that specific regulation of the cerebellar IV/V lobe(PCs )--> FN(CaMKIIalpha+) circuit might provide neuromodulatory targets for the treatment of ataxia behaviors. |
